Mechanism of Calcium Entry during Axon Injury and Degeneration

LoPachin, Richard M.; Lehning, Ellen J.

doi:10.1006/taap.1997.8106

Cited by 153 publications

(88 citation statements)

References 84 publications

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“…This technique permits optical identification of individual cells and analysis of respective subcellular compartments such as the mitochondria and nuclei (LoPachin and Lehning, 1997;Meldolesi and Grohovaz, 2001). Therefore, after samples are rapidly frozen at various time points during the experiment, changes in Ca 2+ concentration can be measured simultaneously in different cells, subcellular regions and organelles.…”

Section: Electron Probe X-ray Microanalysis-mentioning

confidence: 99%

Optical and pharmacological tools to investigate the role of mitochondria during oxidative stress and neurodegeneration

Foster

Galeffi

Gerich

et al. 2006

Progress in Neurobiology

166

135

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Mitochondria are critical for cellular ATP production; however, recent studies suggest that these organelles fulfill a much broader range of tasks. For example, they are involved in the regulation of cytosolic Ca 2+ levels, intracellular pH and apoptosis, and are the major source of reactive oxygen species (ROS). Various reactive molecules that originate from mitochondria, such as ROS, are critical in pathological events, such as ischemia, as well as in physiological events such as long-term potentiation, neuronal-vascular coupling and neuronal-glial interactions. Due to their key roles in the regulation of several cellular functions, the dysfunction of mitochondria may be critical in various brain disorders. There has been increasing interest in the development of tools that modulate mitochondrial function, and the refinement of techniques that allow for real time monitoring of mitochondria, particularly within their intact cellular environment. Innovative imaging techniques are especially powerful since they allow for mitochondrial visualization at high resolution, tracking of mitochondrial structures and optical real time monitoring of parameters of mitochondrial function. Among the techniques discussed are the uses of classic imaging techniques such as rhodamine-123, the highly advanced semi-conductor nanoparticles (quantum dots), and wide field microscopy as well as high-resolution multi-photon imaging. We have highlighted the use of these techniques to study mitochondrial function in brain tissue and have included studies from our laboratories in which these techniques have been successfully applied.

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Section: Electron Probe X-ray Microanalysis-mentioning

confidence: 99%

Optical and pharmacological tools to investigate the role of mitochondria during oxidative stress and neurodegeneration

Foster

Galeffi

Gerich

et al. 2006

Progress in Neurobiology

166

135

View full text Add to dashboard Cite

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“…Alterations in the distribution of another axolemmal component, Na + /K + -ATPase, could also contribute to NMV formation in the Caspr mutant. This possibility is suggested by its proposed role in the pathophysiology of anoxic injury in myelinated axons LoPachin and Lehning, 1997;Stys, 2004). During anoxia depletion of ATP levels in myelinated axons results in reduced Na + /K + -ATPase activity.…”

Section: Potential Mechanisms Of Nmv Formationmentioning

confidence: 99%

“…Such decreases in Na + /K + -ATPase activity may cause disruption of Na + and K + gradients across the axolemma and lead to reverse operation of the Na + -Ca 2+ exchanger located in the nodal membrane. In this model, reversal of the Na + -Ca 2+ exchanger produces an influx of toxic extracellular Ca 2+ LoPachin and Lehning, 1997;Stys, 2004). By analogy, dispersion of Na + /K + -ATPase in the nodal membrane of the Caspr mutant could, by reducing the effective enzyme activity over a wider expanse of membrane area, potentially contribute to metabolic stress and reverse operation of the Na + -Ca 2+ exchanger.…”

Section: Potential Mechanisms Of Nmv Formationmentioning

confidence: 99%

Disrupted axo-glial junctions result in accumulation of abnormal mitochondria at nodes of Ranvier

2006

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Mitochondria and other membranous organelles are frequently enriched in the nodes and paranodes of peripheral myelinated axons, particularly those of large caliber. The physiologic role(s) of this organelle enrichment and the rheologic factors that regulate it are not well understood. Previous studies suggest that axonal transport of organelles across the nodal/paranodal region is locally regulated. In this study, we have examined the ultrastructure of myelinated axons in the sciatic nerves of mice deficient in the contactin-associated protein (Caspr), an integral junctional component. These mice, which lack the normal septate-like junctions that promote attachment of the glial (paranodal) loops to the axon, contain aberrant mitochondria in their nodal/ paranodal regions. These mitochondria are typically large and swollen and occupy prominent varicosities of the nodal axolemma. In contrast, mitochondria located outside the nodal/paranodal regions of the myelinated axons appear normal. These findings suggest that paranodal junctions regulate mitochondrial transport and function in the axoplasm of the nodal/paranodal region of myelinated axons of peripheral nerves. They further implicate the paranodal junctions in playing a role, either directly or indirectly, in the local regulation of energy metabolism in the nodal region.

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“…Thus, conduction of action potential fails. LoPachin and Lehning [27] reported an increase in axoplasmic Ca 2+ in a wide range of experimental nerve injury models which causes acute or chronic axon degeneration. In our study, possible pathways/ /mechanisms to the alterations seen after HI can be the levels of axoplasmic Ca 2+ increase in response to in vitro ischemia in myelinated axons.…”

Section: Discussionmentioning

confidence: 99%

Effects of a Tumor Necrosis Factor-Alpha Inhibitor (Etanercept) on the Sciatic Nerve in a Hypoxic Ischemia-Induced Neonatal Rat Model

Büyükakıllı¹,

Atıcı²,

Ballı³

et al. 2014

Adv Clin Exp Med

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Background. Neonatal hypoxic-ischemic (HI) injury has been considered to have acute and long term deleterious effects on many tissues, including the peripheral nerve. Objectives. In this study, the effects of a tumor necrosis factor-alpha (TNF-α) inhibitor (etanercept) on peripheral nerve damage and the ultrastructure of the sciatic nerve and gastrocnemius muscle in rats exposed to HI during the neonatal period were examined. Material and Methods. In this study, 45 seven-day-old rats were used and they were divided into three groups. The right carotid arteries of the rats in the saline and etanercept groups were ligated and put in a hypoxia chamber containing 8% oxygen for two hours. Just after hypoxia, the etanercept group was given 10 mg/kg etanercept, but the saline group had only saline intraperitoneally. The sham group rats' carotid arteries were not ligated or put in hypoxia. The amplitude, area and latency of sciatic nerve compound motor action potential (CMAP), which mainly reflects axonopathy and myelinopathy, were measured using standard techniques in the seventeenth week following the HI. Sciatic nerve and gastrocnemius muscle were evaluated with a transmission electron microscope, and grading for myelin sheath damage was done to all groups. Results. Neuropathy was seen in rats after HI. While treatment with etanercept showed a protective effect for the axons of sciatic nerve, demyelination could not be recovered with etanercept. Conclusions. This study is the first in literature to show a partial interruption of the signal through the peripheral nerve fibers caused by axonal and myelin dysfunction continuation in rats exposed to HI after birth, in the 17

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Mechanism of Calcium Entry during Axon Injury and Degeneration

Cited by 153 publications

References 84 publications

Optical and pharmacological tools to investigate the role of mitochondria during oxidative stress and neurodegeneration

Optical and pharmacological tools to investigate the role of mitochondria during oxidative stress and neurodegeneration

Disrupted axo-glial junctions result in accumulation of abnormal mitochondria at nodes of Ranvier

Effects of a Tumor Necrosis Factor-Alpha Inhibitor (Etanercept) on the Sciatic Nerve in a Hypoxic Ischemia-Induced Neonatal Rat Model

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